Watch the Replay: Discover the Latest Myeloma Research at ASH — Insights for Patients & Families

Speaker 1:
It is rolling.

Dr. Joseph Mikhael:
All right. Hello and welcome, everyone. This is Dr. Joseph Mikhael, the privilege of being the Chief Medical Officer of the International Myeloma Foundation. We are live with you on Facebook. Over the next couple of minutes, I want you in the comment section and in the Q&A section to tell us who you are, where you're coming from, because we know when we do a Facebook Live, we get patients and care partners and interested parties all over the planet. We are coming to you live. It's not just a Facebook Live in that it's live event. We are coming to you live from, well, previously sunny San Diego. It's now the evening. We are almost at the final day of the American Society of Hematology Annual Meeting. And over the last several days, we have been celebrating the 66th annual meeting that has been held by the American Society of Hematology.

I am surrounded by some of the people in the world that I love the most. We have the myeloma voices here. Who are the myeloma voices? Myeloma voices are patients and care partners that are committed to multiple myeloma and education in myeloma and want to share what they're learning with others. And so every year, the International Myeloma Foundation brings together these amazing people and you'll get to meet them all over this next 40 minutes or so, and they will share with you what they have been learning here at this meeting. They'll share with you some of the questions that have been generated. And I'm very excited to be able to be our host for this evening. We are committed in every capacity at the IMF to answer the questions that you have. Questions maybe that have been generated through ASH over the last several days because maybe you've seen some press releases, maybe you've been seeing all the tweets and the LinkedIn and the Facebook comments that have been going out from the meeting.

But please know if we don't get to your question tonight, we are very interested in answering everyone's question. I have the privilege of trying to answer many of these questions in different venues. We'll have another Facebook Live early in 2025. We're actually also going to take some of the folks that are here. And on January the 8th, we're going to have a dedicated session to learn a little bit more about what are the implications of all this amazing science for patients immediately in the next several months. And you'll hear more about that later on. But then there are other times that we'll just answer some of these questions on video. Sometimes we answer them in less than a minute, so if you have questions, please enter them into the Q&A. My partner in crime here, Jen, is monitoring every question that comes in and we'll try and get to them.

So to tell you a little bit about the order of events tonight, we're going to do a few things. First of all, I'm going to give you the quick Dr. Joe overview of ASH. I'm going to give you the last five days in five minutes. And in those five minutes, I'm going to give you the five topics that I think are the hottest coming out of ASH. And then I'm going to ask every one of our patients and care partners and providers, even here nurses that we have with us, to share with us either a question that they want to have answered based on what's going on here at ASH or a key takeaway that they have had throughout. And so that'll be an opportunity to hear from all of our myeloma voices.

Then we'll take some time to answer your questions and some of the questions of the patient voices that are not necessarily audible here tonight because not only did we bring patients here to the annual meeting, many of our patients have actually been following us virtually and have been going through the process on a virtual method, and so they're going to share some questions with us. We'll answer some of your questions. And then to wrap it up and because he's my boss, I'm going to call on the boss, our president and CEO, Yelak Biru who is a survivor and thriver with multiple myeloma. We're going to ask Yelak to give us some closing thoughts. So everybody who's in agreement with that agenda, sit down. Magic. Everybody's sitting down. So let's get to it. I hope you've told us who you are, where you're coming from so we can learn more. So the American Society of Hematology is really the premier hematology meeting around the whole world. We have had just short of 29,000 people here in person in San Diego, and another three and a half thousand people connecting to the meeting virtually.

And it's an opportunity for the latest and greatest in research to be presented. We had over 8,500 abstracts. And abstract is just a summary of someone's research. These get submitted back in August and then they're reviewed. And hundreds if not thousands actually of them are actually presented here at the meeting. Sometimes they're presented as what we call an oral presentation, sometimes just as a poster and sometimes just in the book. We're going to be focusing mostly on some of the oral presentations, but we're going to hear about a fascinating poster towards the end of our session today that one of our own here, Oya Gilbert, has been involved with. And our CEO has been involved with a poster. In fact, I had a poster this evening and I couldn't get there in time. So my wonderful and gorgeous wife went and presented on my behalf. Thank you, sweetheart. So let's dive into these five topics. I could literally give you 25 topics, but it wouldn't be fair and we'd be here all night.

But five things that I felt were particularly important addressed at ASH this year. Number one, smoldering multiple myeloma, and we'll get into it a little bit more. But as you know, myeloma is typically preceded by what we call precursor conditions or conditions where the myeloma is starting to grow, but it hasn't caused much damage yet. And this is a really important area of work because we want to catch myeloma as soon as possible, but we also want to be careful not to catch it so soon in that we give people treatment that they may not need or ever need. And so between the first precursor condition called MGUS or monoclonal gammopathy of undetermined significance, which is a mouthful, but just basically means someone's got a little bit of bad protein, but it's not doing any harm. And true myeloma, we have this intermediate condition called smoldering myeloma. And even smoldering, we break into bits. And now we've broken smoldering myeloma into low-risk, intermediate risk and high-risk.

And perhaps the most important abstract presented here at ASH was a study of high-risk smoldering myeloma where patients were randomized to either just be observed, which is typically what we do now and watch to see if their disease grows or being given single agent daratumumab. And there's really quite an impressive difference in favor of daratumumab. I'm not sure we're quite ready to change our whole practice and treat all high-risk smoldering myeloma, but it is going to emphasize the need of having an important conversation with our patients. Topic number two was frontline therapy. We had amazing approvals this year from the FDA for quadruplet therapy or four drug combinations. We saw a lot of updated data helping us understand how we use these quadruplets, what's the best way to do it. But we also heard about new combinations coming up front. Some of the drugs that we typically use later because they're only approved later, like CAR-T cell therapy, like bispecific antibodies, we saw them move into the frontline setting in some of these research trials.

In particular, quite a few trials with using teclistamab, the first bispecific antibody we have in frontline therapy. Topic number three, use of MRD testing or minimal residual disease testing. When we started treating myeloma many, many years ago, we never really thought about what's called residual disease or just a little bit left because it was so hard to get rid of most of myeloma. But now with these great therapies, we can get people down to tiny, tiny bits of myeloma, that little schmutz of disease that's left that we want to entirely get rid of and some of our patients have absolutely no measurable disease. And I was fascinated by how many abstracts were incorporating MRD testing into now starting to make decisions primarily to stop therapy or at least to de-escalate therapy. We're not quite there yet comprehensively, but the research was very convincing in a number of settings where we may be able to treat patients for a period of time, get them to MRD and then stop therapy. And give them my favorite drug, nothing, nada. Great drug.

Every insurance company covers it. Everybody's a hundred percent compliance with it. And it's really what we want to do. I say it all the time, "We don't treat myeloma, we treat people. We want people to have the best quantity, but also quality of life." So lots more to hear about MRD. Topic number four, this is very exciting, is all the novel and new approaches that we have in multiple myeloma. We've had CAR-T and bispecifics for a number of years, but it was very exciting to see the new CARs that are coming, the new bispecifics that are coming. In particular one CAR-T cell therapy, anito-cel, that really looks to be incredibly effective with some less side effects that we've perhaps seen with some of the other CAR-T therapies that we have. Still a little bit early, we need a little bit of time. It's not ready for prime time yet. But we've seen new CAR-Ts, new bispecifics. There's one in particular that we're very interested in where right off the start, it's only given once a month. Right off the start, it looks like we can almost always do it as an outpatient.

These are the kinds of things that we think are not only going to help people control their disease, but give them better quality of life, along with a whole set of new drugs, what I call CAR-T 202 and bispecifics 202 to come. Lastly, major topic number five, one of my favorite topics, less is more. What do I mean by that? We've historically used a lot of drugs in myeloma for a long period of time. I commented earlier, MRD may help us reduce some of that treatment, but we're starting to see a lot of treatments using a little less of certain drugs and still having great outcomes if not better outcomes for patients because they're easier on their system. One of them is dexamethasone, part of the down with dex movement that we all believe in where we saw a very important trial only give dexamethasone for the first two months of therapy and then stop it. And well, I think that's going to be a great template for the future as we use less of these therapies.

I could go on and on and on, but you've heard way too much from Dr. Joe already. So very exciting that we're here at ASH. Very exciting to have the myeloma voices. And now I'm going to turn to each of our dear friends that are here and get them to share with us either a question that's been generated in their minds through ASH or a takeaway message that they have for us. And I'm going to ask each of our friends here tonight to introduce themselves when it comes to their turn so you can see the kinds of folks that we have here with us and their passion and their commitment to overcoming multiple myeloma because our goal, our mission, our vision of course here at the IMF is that we want to see people unburdened by their disease, living life to the fullest. So let me turn it over to you, Rob. Not to put you on a hot seat, but you're on the hot seat, brother. You lead us off. Tell us who you are and let's see what question or takeaway you have for us.

Rob Sam:
Great. Thanks Dr. Joe. And by the way, on behalf of my wife, thank you for down with dex. I know I'm speaking for many folks, many spouses. I'm Rob Sam, and I'm a patient and I co-lead the San Francisco Bay Area support group. Dr. Joe, to the point you just made with your top five, there are a lot of new great treatments. As I sat through these presentations and the abstracts, I thought the most important treatment to me is the one I'm on right now and the next one I potentially would be on. Can you talk just a little bit about how you think about helping patients think about the next treatment? And just as important, how do we get to that next line?

Dr. Joseph Mikhael:
Oh, it's such an important question. And sometimes when we sit in a big meeting like this, and with the 30,000 people that are here, despite the fact we're talking about patients all the time, you can sometimes get caught up in the science and lose the present treatment that's going on. And so you raise a really, really important question about how are we best using the treatment that we have now and how are we going to get people to that next treatment? And I think this is one of the things that we're learning so much about in the treatments that we give, especially for things now like CAR-T and bispecifics where there is a learning curve from them, that these are tools are a little bit blunt when we first get them and we have to harness them. And so one of the take home messages I always want to leave with patients is to have that dialogue with their healthcare team to really talk about any signs, any symptoms that they're having. Is there a way that we can optimize the treatment that we're given?

Sometimes it's a little bit less of something, sometimes a little bit more of something else. And a lot of these drugs that we're using in combination, we can make some minor adjustments to them. This is one of the things that reminds me that we really do want all myeloma patients in some capacity connected to a myeloma expert because we've learned a little bit of the tricks of the trade. And then to the second part of your question, getting them to the next therapy is to realize that we don't save the best for last in myeloma. We want the best treatments possible because sadly with every line of treatment, there's some people that don't make it to the next line and so we want to get those. And I know Yelak will talk to us at the end of this Facebook Live about the critical importance of advancing these treatments quickly to the clinic so that people don't hear about these great therapies and say, "It's never going to come to me." Because we need to get them sooner than later-

Rob Sam:
Thank you, Dr. Joe.

Dr. Joseph Mikhael:
Great. All right, let's turn to you, T.M.

Teresa Miceli:
All right. Well, welcome, everyone. Teresa Miceli here. I have the fortunate pleasure and privilege of being the nurse liaison with this group and I also co-facilitate two groups. And my question really has to do with the smolder-bolder group that I co-facilitate with Jesse Dow, one of our other myeloma voices who's covering things virtually or remotely. And there've been a lot of topics related to the approach in managing smoldering myeloma and almost two camps of thought. Are we trying to cure myeloma by treating smoldering? Or are we really trying to prevent maybe the myeloma-induced frailty that can come from an active diagnosis in myeloma defining events? And so we've had some really interesting things on monotherapy dara. We've had CAR-T presentations where there's been a hundred percent MRD negativity out of a small N of people. But these are really compelling discussions and I agree with you. I'm not sure that we're at a point of saying we're going to change everybody with high-risk smoldering myeloma to therapy, but I'm really interested in what your takeaways are on that. And as the co-facilitator, these questions are going to come up.

Dr. Joseph Mikhael:
Yeah, and these are great questions. It's funny today one of the great community doctors I work with closely in Phoenix who refers a lot of patients to me, probably five minutes after the presentation was made for that one study you mentioned the daratumumab versus the standard of care, the AQUILA study. He texted me already to said, "All right, Dr. Joe, what do you think?" So if you're listening BC, now we're talking about you. But to step back for a minute, we use this big fancy word in science, which is equipoise. Equipoise means we don't know the answer to a question and that's why we test a hypothesis, we test a theory. And when it comes to smoldering myeloma, sometimes we as myeloma doctors, we are not willing to accept that there is equipoise. Meaning that we in general, of course we want to catch myeloma early, but we know that so many people in the world have MGUS and many of those people will never develop active myeloma. We don't want to overtreat, but at the same time we don't want to undertreat.

And so I think what these studies are teaching us is that we have to try different strategies to ultimately figure out what is the best strategy. One strategy is just to wait for as long as we think we can until it's very evident that someone has active myeloma. We don't want to wait until they break a bone, until they have kidney damage, or the analogy we've used together, Teresa, is like someone running towards a cliff. I don't want to wait until they fall off the cliff, but if the cliff is miles and miles away, let them enjoy their run. So where do you intercept that person, right? So we want to intercept them early enough, but not too early. On the other hand, it may be that a single agent like daratumumab, we've had it done before with Lenalidomide where you've even mentioned that we've done it with CAR-T or bispecifics and sometimes there was another study here looking at two drugs together.

We don't know if in the very long run that might prevent someone from ever getting myeloma or kick the can so far down the road that they enjoy a quality of life for 10 years before their myeloma becomes active. When their myeloma does become active, does it become super myeloma and very difficult to treat? We don't know yet. From the preliminary data of this meeting, I think we're going to see that some patients may opt to be treated for high-risk smoldering myeloma. I think it comes down to the importance of that discussion with the patient where we look at the pluses, the minuses and decide together. But the field at large is still needing to grow. I don't think there's a massive tidal shift after this meeting that we're going to start treating everybody high-risk smoldering myeloma. And we definitely don't want to over treat the people that have lower risk smoldering myeloma.

But I do think there's a legitimate argument to treat them based on the data. But there's also a legitimate argument to say we haven't fully answered the question and we want to continue to watch. And so I think it's really important that that discussion be had. My last point on that would be that I think we still have a little bit more to learn about how we define high-risk smoldering myeloma because that's why I give the analogy of running to the cliff because it's both the distance to the cliff and how fast I'm running. And right now most of the measures we use are all about the distance and not about the speed. And so we have some people that may look like they're relatively close to the cliff, but they're like me, a cliff runner, and they run along the side and they're never going to cross that. And we want to be careful. Our oldest adage in medicine is above all do no harm-

Teresa Miceli:
Do no harm.

Dr. Joseph Mikhael:
And I don't want to overtreat people, but I surely don't want to undertreat them either. As expected, amazing question, T.M.

Teresa Miceli:
Well, and really important point about including the patient voice, hence why we're here and having an informed decision that goes with it.

Dr. Joseph Mikhael:
Absolutely. I think you've said that so perfectly. You don't want as a doctor to say, "You'll take it and you'll like it." You've all heard me say that joke before. That's not what we do. All right, professor Tuohy.

Michael Tuohy:
Okay. Hey, everybody. Michael Tuohy here. I'm a 24-year myeloma patient and we run a support group in Prospect, Connecticut. So Dr. Joe, my question for you is, can you comment on the mechanism of action of an intent to make but formerly have the 383?

Dr. Joseph Mikhael:
Wow, you got the words right. You got the-

Michael Tuohy:
Like that?

Dr. Joseph Mikhael:
Words right. Well done, brother. Well done. Okay. That's great. So if people aren't familiar with this drug, it is one of the newer bispecific antibodies, as we call it. So to remember, bispecific antibodies are called bispecific because they have two arms to them. One arm hooks onto the myeloma and one arm hooks onto a local T cell and engages that T cell, as we call it, or activates the T cell to destroy the myeloma. So it's a drug that we just directly give to patients. We don't have to pre-collect their T cells like we do with CAR-T. We have three approved already bispecific antibodies, teclistamab, elranatamab, and talquetamab, and we have others soon to be approved. But you saw the presentation that I did, Dr. Rodriguez presented it from Sinai. A beautiful presentation that this is a newer bispecific that has a few different features to it.

On the practical side, it's different because it's pretty much just given once every four weeks from the very start, as opposed to a lot of the ones we start at once weekly. Number two, it has either none or maybe one step-up dose. So often we give what are called step-up doses, meaning small doses to get the body adjusted to the drug because it interferes appropriately but interferes with our immune system. Sometimes our immune system can overreact to bispecific with something called cytokine release syndrome. So a lot of the other bispecifics have that, but it has less of it. And because of that, the drug is primarily given in an outpatient setting. So on the clinical side it's very fascinating. So part of the understanding is... Or part of what we need to understand is why is that happening? And you've mentioned it in your question, which is, is there something different about the mechanism of action?

And I like how Dr. Rodriguez described. He said that the drug is almost like it attaches to the T cell but doesn't bind it so tightly that it squeezes the life out of this poor T cell. He called it the Velcro effect. It sticks to the T cell so that it engages the cell, but then lets it go so that T cell become a persistently active phenomena that may lead to the cytokine release syndrome or may lead to other complications. I think we still need to understand that mechanism a little bit more, but it was very encouraging to me that the data was very good from it. Obviously it's a little bit further down the line than some of the other bispecifics. But I'm very excited about this molecule because I really think it's going to be an opportunity to treat patients primarily as an outpatient with perhaps less risk of some of the side effects we see now. So great question.

Michael Tuohy:
Thank you, Dr. Joe.

Dr. Joseph Mikhael:
Right. Turn it to your boss.

Michael Tuohy:
My boss.

Dr. Joseph Mikhael:
I mean to our boss.

Michael Tuohy:
She's my boss.

Dr. Joseph Mikhael:
Yeah, she is.

Robin Tuohy:
No. They're silly. I'm Robin Tuohy, vice president of patient support at the IMF. I co-lead our Prospect, Connecticut group and a care partners group as well. So quality of life we all know is so important and I was really interested in a phase three French study for frail people. And so frail patients really have less options sometimes. And this study was with dara and Revlimid versus Revlimid and dexamethasone, our old friend dex and down with dex. So it was really interesting, I think, that the dara/Revlimid arm showed less progression and also less death, which is a good thing, right? And I think it was a 49% reduction in progression or death. So, let's talk about that a little bit.

Dr. Joseph Mikhael:
Yeah. Well, I mean, it's a fascinating study for a lot of different reasons. This is from our friends in France, presented by one of our very good friends, Salomon Manier. And the short version here was fascinating, was that they designed a trial from the very start knowing that... Although as I say dexamethasone, we love because it has an anti-myeloma property, it helps reduce certain side effects like nausea and pain and infusion reactions. But we all hate dex. We've already heard from Rob that his wife is not the biggest fan of dex, right? When I talk to my patients about dexamethasone, I don't look at them, I look at their spouse, right? To see. But they wanted to see, can we just give dex for the first two months? And it was really remarkable how well these patients did with it. And I think it's very sentinel to our down with dex movement, but it's more than a movement. It's really trying to optimize the benefit of dex.

The way I described dex sometimes it's, it's like the booster rockets on the shuttle. It does help at the start, but eventually it needs to fall off because especially with these combinations and they showed in that study with that triplet really of daratumumab, Revlimid and dexamethasone, although the dex got shed pretty quickly, they were able to even give it to frail patients who we've historically really worried about giving dexamethasone to. And we had a great discussion at our International Myeloma Working Group breakfast around this notion that, hey, if it works in that context, maybe we should be doing this in other contexts where we use less dexamethasone and stop it after two months. And I think that's coming. So, fantastic question. Thank you, Robin. All right, let's come over to Terry who's next. Jen's here, still monitoring all the questions. We'll come back to you, buddy. Don't worry.

Jen Wieworka:
Okay.

Dr. Joseph Mikhael:
Terry, Terry.

Terry Glassman:
Terry, Terry. Hi, everyone. I'm Terry Glassman. I am an IMF support group leader from Long Island, New York, and I'm also a research nurse. And so Dr. Joe, as being a prior research nurse, I was excited to see something change the standard of care. So the quad therapy changed standard of care. So I'm very interested in hearing you talk a little bit about daratumumab and isatuximab, if you would.

Dr. Joseph Mikhael:
Absolutely. So it was pretty amazing in one year to have two, I would say, very influential shifts in standard of care as you've described in our FDA approvals. Earlier this year, we had an FDA approval of using daratumumab plus VRD or Velcade, Revlimid and dexamethasone in patients that were going to stem cell transplant. And then in the middle of the year in July, we saw isatuximab plus VRD approved for patients who were primarily not going to transplant. So almost as if it were quads for all or four drugs for all. Not that every single myeloma patient will get a quadruplet, but the vast majority will. And so it does raise the question often, is there a big difference between daratumumab and isatuximab? And I've had the privilege of being involved in both of these molecules and isatuximab in particular. And I think the short version is that most of us feel these drugs are very similar and they act in a very similar way. And they're not entirely interchangeable but similar.

And there are some differences in the way they're given. Daratumumab right now is given subcutaneously mostly. Isatuximab, given IV but will soon have a subcutaneous formulation. There's a little bit of a difference in the dosing. But you make a really good point about the standard of care that if we have patients listening tonight that are newly diagnosed, that this needs to be had as a conversation with your healthcare provider that really the new standard is a four drug combination with one of those CD38 antibodies, be it isa or dara, plus the VRD combination. Sometimes we adjust the doses based on patients, sometimes we have to make some other adjustments. But what an exciting shift in standard of care. And this ASH really did demonstrate a lot of other studies continuing to emphasize the importance of those quads. Great question, Terry. Thank you.

Terry Glassman:
And we're so grateful for it.

Dr. Joseph Mikhael:
Sherry, Sherry. Terry to Sherry.

Sherry Baker:
That's right. That's right. So I'm Sherry Baker, I'm a 13-year myeloma patient and I lead a support group in Boise, Idaho. So my question, Dr. Joe, has to do with the DREAMM-7 Trial and the data that they showed with the benefit of Blenrep with Velcade and dex over potentially better than daratumumab and Velcade and dex. But Blenrep comes with the ocular toxicity, blurry vision and those issues. And for me as a patient, I mean, your eyes and your vision, that's huge and that's worrisome. So what should patients be worried about or how worried should they be if they consider taking Blenrep?

Dr. Joseph Mikhael:
Yeah. So great question and one that is going to be discussed a lot because we really actually do expect because of that DREAMM-7 and another DREAMM-8 study when it was combined with pomalidomide, dexamethasone that will quite likely get this drug back in the clinic this coming year in 2025. It's still there to a certain extent, it just has to be in a very special way because it was removed from the market because of some earlier trials. And what I would say to patients is I want to balance optimism with realism. The optimism is these studies were amazing. Three drug combinations versus another three drug combination that really showed a massive benefit. There is no doubt that this drug works. Also, it works in a way like our CAR-T's and bispecific works with a target of BCMA, but we don't have to collect T cells, we don't have the risk of cytokine release syndrome. So it's very, if you will, easily administered. But realistically, it does come with this ocular issue where people, as you mentioned, can get blurred vision.

That being said, we are capturing now a lot of data because we've been using the drug for a few years that actually when we use the drug less frequently, somewhere between every eight and 12 weeks, we've seen significantly fewer of those eye events. And looking forward, we actually really think that's almost definitely the way we're going to be giving the drug. So if you're a patient, and this is something that in this coming year your doctor's suggesting to you, there are some steps we're going to have to go through to, no pun intended, keep an eye on how things... I know. I'll keep my day job. I got it. But at the same time, we really believe that this drug, when given less frequently, what's encouraging is not only do we see less of the eye issues, we actually still see the response maintained in patients that have responded. So I think it'll be a much smoother ride this coming year for belantamab or Blenrep than it was last year.

Sherry Baker:
Oh, that's good to know.

Dr. Joseph Mikhael:
Thank you, Sherry.

Sherry Baker:
Thank you.

Dr. Joseph Mikhael:
Turn it over to that character next to you.

Jimmy Shoemaker:
I just appreciate the fact that you say that we got these great questions. I thought I was supposed to memorize my question. It took all day to get my question, so I got it memorized. It's what we've been doing, right? Though. I'm Jimmy Shoemaker from Memphis, Tennessee, lead a support group there and I've had myeloma for 17 years. And I'm blessed to know this man and I so much appreciate what he does, and also what the Myeloma Foundation does. So thank you, sir. I've been through talquetamab which is a trial and I've just got through that ending of that stage. But I was introduced to something called IVIG. And then I had not heard of IVIG and it was my IGG number was low. And of course, what we've learned in this whole process is the number of infections that patients have to be very careful with and doctors managing that. And that's something that I've been, of course, paid to close attention because in my last 16, 17, 18 months, I've had some infections that I've never had before and just never thought about having.

I've been blessed with a great doctor in Memphis that pays attention to that and says, "It's time for you to start IVIG." So I'd like for you to just talk about that. Is that where we're headed, where patients are going to just have to be sensitive with their doctors that IVIG may be just a part? And I guess explain what IVIG is.

Dr. Joseph Mikhael:
Sure. No, absolutely. A great question. So very quickly-

Jimmy Shoemaker:
See, he said that? He said great question. It took me all day to memorize it.

Dr. Joseph Mikhael:
I'm glad you memorized it. You memorized it well. So IVIG stands for intravenous immunoglobulin or IG for short. So just as a quick recap, we remember myeloma is a disease where the plasma cells in our bone marrow become cancerous. Plasma cells, their job when they're not cancerous is to make immunoglobulin or sometimes we call it antibodies or even sometimes we just call them proteins. These are the antibodies that protect us against infections. If I go get my flu shot or if I get a Covid shot, that message gets sent to my plasma cells. My plasma cells make immunoglobulin that is specific to the flu or to measles, mumps, rubella, whatever else it might be. So as we treat myeloma or when someone has myeloma, they're at greater risk of infection because already the cells that are supposed to be making good immunoglobulin now become cancerous. So the fraction that are making good immunoglobulin tends to go down.

To add to that, when we treat someone, and this is why it's become an issue now, Jim, is that we are now treating people with very, very effective therapies that wipe out plasma cells. The problem is they don't only wipe out the bad plasma cells, they wipe out a little bit of that fraction of good ones that are left because they're so effective. Think of it almost like friendly fire. It knocks out the good plasma cells and so people's immunoglobulin levels go down. And we've seen low immunoglobulin levels with CAR-T and bispecifics more than we've ever seen before. We didn't quite anticipate that much. And that's why we're rushing to get so many of our patients onto IVIG right now. That being said, looking forward, it's a bit of a pendulum swing, right? Every drug that gets introduced to myeloma, we learn about and we get better at managing it. Right now, we're very aggressive to give patients IVIG, to talk to them about knowing what to do when you get a fever, knowing what to do when you have signs or symptoms of an infection.

But I also want to be a bit more optimistic to the future that I think we can generate with time these therapies, finding the right dose of them and giving them in such a way that maybe we don't wipe out as many of the good plasma cells. But in the short term, while we're figuring that out, it's very important for all myeloma patients to know what IVIG is. The majority of myeloma patients still don't need IVIG. It really is a small fraction of patients that have gone through these treatments. But it is almost everybody who's on a bispecific and almost everybody who's been on CAR-T for at least a period of time. But it's good to know about it so that when they're on those therapies, they can be treated appropriately.

Jimmy Shoemaker:
I appreciate you saying that. And what I want everybody to understand, this has been a phenomenal conference. I've been to a lot of conferences. When I was in college, I took up organic chemistry. When I went into the class, they said, "If you drop your pencil, drop the class." I dropped my pencil three times a day, I dropped the class. It's amazing how much information we're exposed to.

Dr. Joseph Mikhael:
There is a lot of information here. I'm glad you enjoyed it. All right. So last of our live characters here is Oya. Introduce yourself, brother and let us know what you learned or what you contributed to this meeting.

Oya Gilbert:
All right. My name's Oya Gilbert. I am a multiple myeloma patient since 2017 and I have a support group in Hagerstown, Maryland. One of the cool things about the International Myeloma Foundation and being one of the myeloma voices is you get an opportunity to do things that you've never done before and be the importance of your voice. So I'm actually here not only to get the new information, but I was also blessed to be a part of doing a poster presentation for the first time. So my first year attending ASH was last year. So this shows you the power of our voice. So a year later, I got an opportunity to be the lead author on a poster called A Patient's Perspective on Actionable Steps to Addressing Disparities in Healthcare Amongst US Patients With Multiple Myeloma. And so that particular publication had two other authors from the International Myeloma Foundation. One was Jack Aiello, and so rest in peace to him. He was a huge contributor to the myeloma community. And Jim O'Mell, he also was one of the patient authors.

And so that's what was really unique about this particular poster is it was completely patient driven and that's what we really loved about it. There was healthcare providers involved and also industry partners, but we really, really dictated it from a patient standpoint of what was going to be... Not only what we decided to address, which was the two main things that came out was, one, was the access to care for rural areas and the representative communities, and the others was the disease specific treatment for patients and understanding that. So now that it's so many things and got smoldering myeloma and then of course, you have multiple myeloma itself, there's different phases in how that should be treated. And so that was one of the cool things. And one of the biggest things that came out, it was telehealth or telemedicine. One of the things that came out of Covid was it works. It really does. But as the funding has been diminished from having all of that Covid, you don't have telehealth in all of the states anymore.

We know it's a big task. However, if we don't start addressing some of the giants or elephants in the room, we'll still be talking about moving the needle 20 years from now. So it was just really great to be a presenter of that poster, Lee authoring it. And so I'm just really excited that we got a chance to be a part of that.

Dr. Joseph Mikhael:
Well, thank you for being with us tonight, Oya. And thank you for being a part of that. I mean, you raised so many issues. It's hard for me to add much more to that. But know the IMF has been so committed to this as we've created the Empower Program and everybody on this couch has been a part of that in different capacities and ways to improve the short and long-term outcomes of African-Americans with myeloma, but also all those that have been underrepresented and undertreated, frankly, in many respects in multiple myeloma. And thank you for being such a powerful voice to raise the significance of health disparities and our desire to reduce them. And there was quite a bit of great work here as we... Even in my role at ASH, something we've had a very strong feeling about and have decided really to encourage all authors in each of their presentations in each of their work. We don't just want studies that specifically look at disparities. We want to look at the concept of disparities in all studies.

We want people to report the appropriate demographics of the patients on their trial and what steps they took to improve representation within their trial. So thank you for being that voice. All right, Jen, you're up now. I know we've only got about seven minutes left because we're going to go to Lacqua after. But in those last seven minutes, let's take a question or two from our online myeloma voices and then maybe some from the crowd. And I'll promise I'm going to answer questions in less than 60 seconds.

Jen Wieworka:
Okay. So first I'd like to introduce myself. My name's Jen Wieworka. I am a nurse and a director of support groups with the International Myeloma Foundation. And I focus-

Dr. Joseph Mikhael:
In her first year.

Jen Wieworka:
It's my first year, my first time at ASH. And I am in the Midwest region. So from our virtual team I think that we're going to go with because this was just such a conversation starter and meant a lot to, I think, all of us in different capacities. From one of our team members, Barb Davis, does the UPEP research, which has to do about the little brown jug urine collection 24-

Sherry Baker:
Big brown jug.

Jen Wieworka:
The big brown jug, yeah. 24-hour urine collection, mean those of us that don't have special conditions like Bence-Jones protein uremia can gently suggest to our Docs that we do not want to do the 24-hour urine anymore?

Dr. Joseph Mikhael:
We're getting pretty close to that. Again, short version is that this was a great study led by one of my mentees, Rahul Banerjee, who joined us for lunch today. So myeloma, as we mentioned, is a disease of the plasma cells that releases that immunoglobulin. We typically measure it in the blood, but we can also sometimes measure it in the urine. And historically in myeloma, we always wanted to measure both and even our criteria for depth of response in someone was you needed both to be done. And he did this study saying, "Do we really need to do the urine? What if we exclude the urine from our testing, do we still have robust response data and is it appropriate?" And basically showed that it was appropriate. And in our new IMWG criteria, we're going to not entirely remove, but significantly minimize. So I don't think I can tell that patient that tomorrow you got to absolutely stop doing urine, but we're going to be doing a lot less of that urine testing, especially that ugly orange, 24-hour urine bottle.

Jen Wieworka:
Yeah. And so here's another question from our online viewers. Someone who started DRD in March, they're now on maintenance with Rev and Dex or Darzalex, and they were wondering if Darzalex alone is okay for maintenance with no stem cell transplant because they're getting neuropathy from the Rev.

Dr. Joseph Mikhael:
So great question. So we've learned, as we mentioned earlier, we're moving towards quadruplets, but there are still a lot of triplets that are in use that we don't now immediately change someone back to a quadruplet if their treatment has been working. And one of the most common triplets in people not going to transplant is getting Darzalex or daratumumab plus Revlimid or it's also called lenalidomide with some dexamethasone. Sounds like the person continued them, the two that we would normally continue, Darzalex and Revlimid, but is having some symptoms from the Revlimid. And I said it before, I don't treat myeloma, I treat people. And it's really important for us to have that conversation with a patient about symptoms they may be having. Neuropathy is one of those things that can happen. We typically of neuropathy maybe more from Velcade, but we sometimes do see it from Revlimid. So obviously it's hard for me to answer very specific questions about one patient because you want to discuss this with your healthcare provider.

But in general, if someone is on daratumumab and Revlimid and one of them has to stop because of a side effect, yes, I would continue that Darzalex. I wouldn't stop both because the Darzalex by itself will likely keep that disease in remission longer before they have to be treated again. Let's take another question or two, and then I'll call the big boss in for his final thoughts.

Jen Wieworka:
All right. So here's one that I know can affect a lot of patients. Someone that has myeloma and amyloid affecting their kidneys, and nephrologist is considering dialysis. They're concerned about how much their body can take before starting new medications.

Dr. Joseph Mikhael:
Yeah, that's a tough situation. So amyloidosis really in some respects is a cousin disease myeloma, but sometimes can coexist with myeloma. So we sometimes make a distinction, does a person primarily have what we call AL amyloidosis or do they have multiple myeloma? But sometimes they can coexist. And so that conversation has to be had very carefully and very careful testing has to be done. And we commented earlier about sometimes this is where it's particularly important to have a myeloma specialist on your corner to try and help make that distinction. Sadly, with the way amyloidosis works, it can very much damage the kidney, and so it may influence what treatments we can give. That being said, the vast majority of treatments we have in myeloma, we can actually still treat people when they're on dialysis, believe it or not. We've had some important work even presented here at ASH around giving CAR-T cell therapy when on dialysis, giving bispecific antibodies.

It does require a little extra attention, some adjustment and dose adjustment and so on. But we want to try to provide the best care possible for that individual and so that obviously has to be followed up a little bit more closely with their healthcare provider. But a great question.

Jen Wieworka:
Okay. You want to take one more?

Dr. Joseph Mikhael:
I think I should give time to the boss.

Jen Wieworka:
Okay. Sounds good.

Dr. Joseph Mikhael:
So remember, I will remind everybody that if you have more questions and we've seen them stream in here, which is amazing, we will work to answer as many of them as possible in our future endeavors at the Ask Dr. Joe Anything, the Facebook Live, in our videos, on our website. And let me put one last plug-in before I bring the boss in. There's someone else who likes to answer questions. It's not just about Dr. Joe. I have this other person who actually works 24/7 and their name is Myelo. And Myelo is the IMF's chatbot, which is available to you 24/7 at myeloma.org. And you can ask Myelo anything, anything related to myeloma of course, and Myelo is there to help you and support you. We have our info line that you can reach through our website that Teresa oversees and we have the opportunity to connect with a human individual as well as Myelo, although Myelo is pretty close to a human, and we're there to answer your questions. Okay, boss, I'm turning it to you to bring it home for us.

Yelak Biru:
I'm here right next to you, Dr. Joe.

Dr. Joseph Mikhael:
Yes, I see that creepily over my shoulder.

Yelak Biru:
So thank you for summarizing five days of ASH in five minutes and five points, and then explaining it in 45 minutes, Dr. Joe. So thank you for that. And so in this group we have patients, caregivers, as you mentioned, providers that have joined us for this meeting. Some of them are joining us for the first time. Some of them are joining us for their 20th time attending ASH. I just looked up when I first attended ASH. It was 18 years ago. And I remember coming to Orlando and going with Robin, and I was very impressed by how detailed every minute of the day was scheduled. And fast-forward 18 years later, every minute of the day is, again, schedule for you. So over the last five days, I have attended many meetings. I have listened to many people. And Dr. Joe summarized the medical aspect of what has happened here.

The two takeaways I have for me is one that he mentioned earlier, which is there are so many brand new therapies that are coming to market. How do we ensure they actually get to the communities? 80% of myeloma patients get diagnosed and get treated in the communities and actually die without actually having the opportunity to have access to these therapies. So we have to do more and we have to work harder in order for us to be able to do that. As more and more therapies become available as well, we as patients and care partners have to play a bigger role in ensuring we are able to articulate our quality of life needs and we are able to actually communicate what we need from these therapies, which means that whether we like it or not, we have to elevate our understanding of multiple myeloma and how the drugs affect that.

I think I'll leave it at that for now. We will have more conversations around all of these topics and IMF strategies and everything that's coming. And I want to close by telling you that next year IMF will be celebrating its 35th anniversary. On October 18th, 1990 was when IMF was incorporated but next year we'll be celebrating our 35th anniversary. More to come on that. With that, I want to thank the person behind the camera, Jason, who has really been following us around all week. And Peter, Sylvia, Liza, who is in the back there, and also Dr. Joe's better half, Emily, who's sitting in the back.

Dr. Joseph Mikhael:
Absolutely. Thanks, everybody, so much for joining us. We will see you soon. Don't forget to come visit us at myeloma.org and hear about all the things that are coming.